Phase III RESONATE-2 That Compared Ibrutinib To Chlorambucil In > 65 Year Old Treatment Naïve Patients Excluding Those With Deletion 17p

Take Away Points:

• Ibrutinib is superior to chlorambucil for frontline therapy in those treatment naïve patients >65 without deletion 17p.
• This could be an important step towards a broader approval and use of novel agents in treatment-naïve patients where the results are superior.

RESONATE-2 Trial:

It is no surprise that ibrutinib is a better therapy than old school chlorambucil. Almost any modern CLL therapy is better than single agent chlorambucil.

The importance of this study is its implications down the line.

By the way, to their credit, the designers of the trial excluded those with deletion 17p as the randomization to the chlorambucil arm would have been unethical. Traditional chemotherapy has no role in these difficult to treat patients

Trial Design:

Here is a simplified link that explains the trial design: http://www.btktrials.com/resonate-2

All the trial’s details are here.

Trial Results:

What they found is ”that ibrutinib (IMBRUVICA®) improved progression-free survival (PFS; primary endpoint) and multiple secondary endpoints including overall survival (OS) and overall response rate (ORR) in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL, respectively) in the final analysis of the Phase III RESONATE™-2 (PCYC-1115) trial.”

The press release is available here

This is, as expected, as impressive difference.

Trial Significance:

The importance of this Phase III trial is that it is an important step towards approval of ibrutinib as frontline therapy for those of us over 65 years old. That is what Phase III trials are designed to do.

My hope is that this is the slippery slope that leads to ibrutinib being increasingly available to all CLL patients, regardless of age or deletion 17p status. As a frontline option, ibrutinib clearly does better than in the relapsed and refractory patients, but it also blazes a path for idelalisib and other the emerging therapies to follow to become more accessible to treatment-naïve patients.

We owe our thanks to all the patients who volunteered for this research.

Brian Koffman 6/8/15